Unusually high concentrations of ketone bodies (i.e., ketosis) have been observed in plasma of suckling rats. These elevated levels of ketone remain high throughout the lactating period but drop after weaning to a lower level similar to that seen in the adult rat. Since about 70% of the energy supplied by rat milk comes from fat and 7% from carbohydrate, oxidation of fatty acids has been considered a major contributor to ketosis of suckling rats. The regulation of ketogenesis in livers of starved and diabetic animals has been studied extensively, and from these studies it is clear that an increased influx of free fatty acids into the liver is not a prime factor in controlling the production of ketone bodies. The overall objective of this proposal is to determine the regulatory mechanisms of ketosis in the rat during the suckling period. We will first investigate the relationship between ketone synthesis and activities of ketogenic enzymes, between ketone utilization and activities of ketone-utilizing enzymes and between hepatic metabolites and ketosis. Subsequently, we intend to determine whether the observed ketosis can be reversed by administration of various antiketogenic agents. Finally, the effect of ketone metabolism of dietary fats (medium- and long-chain fatty acids) fed to dams during gestation will be investigated in newborn rats. Data from these studies should increase our understanding of ketosis in newborn mammals, including man, and might enable us to develop ways of controlling ketone concentrations in newborns. Such regulation could be highly beneficial if elevated levels of ketone are critical to energy metabolism in newborns.